他汀类药物与其他药物的相互作用_邓万俊

(ChinJNewDrugsClillRem),20062,25210077669(2006)02013106(,421002)〔〕COA;;;;〔〕33A(HMGCoA)(),。P450(CYP)3A4、、、,,CYPZCg、,。CYP,。〔」R97.26[〕AProgressindruginteraetionswithstatinsDENGWanjun(Deartme,;tofCardiolo,11edNanhuaHosit、zhuaUni、esritJ,He〕aHNA421002,China)KEYWORDS〕rhabdonlyolysishydroxymethylglutalCoAreduetaseinhibitors;statins;druginteraetions;museulardiseases:ABSTRACT]DifferentpharmaeokinetiesexistamongHMGCoAreduetaseinhibitors(statins)prorokingvariousmeehanismsandextentsofdurginteraetion.Lovastatin,simvastatin,atorvastatinandeerivastatinaremai-:llymetabolize(1,,iatlleeytoehromeP45O(CYP)3A4pathwaywitheommonoeeurreneeofdurginteraetionsTllewolrdwidewithdarwalofeerivastatininAugust2001beeauseofitsassoeiationwitilaftalhrabdomyolysis.Fluvastatinandrosuvastatinmetabolisedbytheeyro(hromeCYPZCgexhibitvelowpropensitiestoelieitmyopathyeombiningwirhorheragents.rPavastatindoesnotmetabolize:iatheeytoehrome4P5Osystem,andalsowellpossessestoleraneewithrareineideneesofmyopathyandabnormalliverfunetiontest.33A(HMGCoA)(,SatitnS),(LD)L、(HD)L,。(lovastatin)、(Simvastatin)、(fluvastatin)、(atooastatin)、(pravastatin)、(eerivastalin)、(rosuvastatin)、(pitavastatin)。、、,。。,,1/2。,(FDA)1990-【」20050803【」20051209[](1943),,,,,,[]。phn:867348358342(ChinJNewDrugsClinRem),20062,25220023,3339,58%。,,1680[2],20018131〔2742,.69%l’]。,,。-HMGCoA,,,,。,,、、、,t,(。~)、、、,,,llsl。l1JJ1J33720,111、/23l、l/g·L12766/12/.8。90Cl,34448192999240.91.10204555)95CYPZCgCYP3A4.3~2.4103459498CP3A411:/}/,/%15~3005~27090;:43~5588CYPZCgO%)()/.32.820.82010719023l358,P450(CYP)。、、CYP3A4,CYPZCg,CYP3A4CYPZCS,CYPZCg。,CYP,CY3PA4161。CYP45O。CYP450,CYP450,。,、、CYP3A4。CYP3A4:、、、、;CYP3A4:、、、、、、、、、、、、、、、、、、、、。、()CYPZCg。CYPZCg:、、、;CYPZCg:、、171。,CY3PA4,70%_4}。CYP4501CYP450CYP450,,,,。,(ACC)/(AHA)4:(1)(sattinmy-opathy)。,,。(2)(myalgis)。,(CK)。(3)(myositis)。I,CK。(4)(htabdomyol-yiss)。CK,10,181。,19971120003,FDA601,36%,32%,12%,12%,7%,2%。1990ll2002331,Osean3339,(57%),(18%),(12%)。.78%。,:1000.。、1%5%。1.1,,,。CY3PA4,、、,,。5lJ。(ihCnJNewDrugslCinRem),20062,252,。,,(AU)C:AUC20,3,.74,3.1,.72,7.1。CY3PA4191。ALERT(AssessmentofLeseolinRenalTransplantation),1000,,,,,}’0]。1.2[91,CYP3A4,、、。,CYP,,!”}。1.3、,。。、、。1,,。1.4(HIV)HIVHVI,,。HIV(nelif-navir)、(ritonavir)、(saquinavir)CYP3A4。HVICYP3A4,、、{`3,`4}。HIVHIV,,。。、。、,。,。(indinavir)CYP3A4,CYP3A4l5[]。1.5,。(mibefraidl)CYP3A4,,。CY3PA4,4。4。,、1161。CYP3A4,HeartProteetionTrial,1.6(fluoxetine)、(flu-voxaniine)、(neafzodone)、(sertra-hne)CY3PA4。2。,(paroxetine)(ven-lafaxine),CYP3A4191。1.7,RCYIPAZ,SCYPZCg。CYPZCg,,,}’71。FDA,}’8}。,(aeenoeoumarol)(fliunidone),,(INR)l’91。1.8(,conju-gatedestorgen)CYP3A4,CYP3A4,。CYP3A4,、、,,。(danazol),,l2(j]。1.9(grapefruitiuiee),CYP3A4,CYP3A4。,1200mL,3,d340mg、200mL,30min90imn200mL,。,AUC。~20。,AUC。~169,AUC.33。。(ChinJNewDurgsClillRem),20062,252,Zh,1[qua,t,1quart=1.lolL()1[9,2`]。1.10CYP3A4,ROTENl21zl,,CK40392U·L,。,,,。2CYP450CYP45O。(troghtazone),C1231。CY3PA4、l5]。l36,0.12%l。CK,,、、、,1251。,。P45O,。,,。,,、、、。,,。,。,。:、,LDL.26mmal·L,,HDL1.0mmol·L,()5.6mmol·L,;、;;、4P5OCYP3A4。,。tl。,9[]。,,。2,,3m。c1K261。2P(P-glcuorPotien),,,、、、1271。P-,,,。,P,,。80mg·d,.025mg·d,20d,;10mg·d,。,,,l28]。3,、、,、1291。4,CYP3A4(dogerl),。,LAU30l[CY3PA4,。,CREDO(ClopidogrelfortheReduetionofEventsDuringobservation)、、、、、l3]]。CYP3A4CYP3A4,32[34]。,,。,、,,。,CY3PA4、、,CYPZCg、,CYP136(ChinJNewD,,ugsClinRem),20062,252resultsfromtheinteraotionsrudy[J].ArellIntel1Med,2004,164(18):20512057.〔34〕Ml)KHEEED,KLINEROGERSE,FAN(J,eraekofolop-i〔(》greCYP3A4statininelaei()12inpatien[5witha〔.ureeorola]、yll({r〔,me【JI,Hea,200591l):2326.「35](leANGEllSGTheinflt,enceofstatilleharaeteristi(5ontheir、afetyandt。,lerability].InLJClinPluet,2004,58(10):945955.[36DAVIDSONMHC〔):.tl()veroy、t,。:J,,。11119thesty。,f(、e“vastai,lljl.Expert()Pi,1DurgSaf2002,l(3):207212.〔37〕CHENGJWRosuv:tstatillintl,enlana“erne,1。,fhyl〕ellipld。,11ialJ!ClinTher,20()4,26(9、:13681387.〔」10077669(2006)02013604(,200011)[1;,;;;;[1()。。,2,。[]R544.l;R972.4[〕AUsingseleetivealdosteroneantagonistintreallltentofhyPertensionHUANGZhenhua(Cordio:aseularReseacrhRoom,,heiNnrhePle3Hos1211edtoMedieoClle,hSanghiJaotongU-uni:esriz),5NGHAI20001],hCina)〔KEYWORDS〕aldosteorneantagonists;reeeptor,aldosterone;hypertension;erninangiotensinsystem;spiron-olaetone;ePlerenone「ABSTRACT〕Theeombinationofaldosteroneanditsereep*orleadingtoinereaseofsodiumandwaterretell-tlonnotaggravatehypertension.Aldosteorneereeptorantagonistmaydividetotwotypes:seleetiveandnonseleetive,onlyhelptoredueebloodPerssuer,butalsodeereasetheadverseeardiaevaseulareffeetsofaldosterone,ear-diaeventieularhypertroPhyandoeeurreneeofeardiaevaseularevents.,(reninan-giotensin。ystem,RAS)。4RAS:(1)。(2)(angiotensineonvertingenzyme,ACE)。(3)11(angiotensinn,AlTl)。(4)()。[]20050714[]20051231【}(1952),,,,,」:,,、、。[】。Phn:862163138341,ex:5341